Calcium phosphate-coated composite material and process for production thereof

ABSTRACT

A calcium phosphate-coated composite material is disclosed, comprising a metallic substrate, an oxide layer on the metallic substrate, said oxide layer consisting essentially of the oxide of one or more metals selected from the group consisting of titanium, zirconium, hafnium, niobium, tantalum, tin, cobalt, aluminum, chromium, molybdenum and tungsten, and a coating layer of calcium phosphate provided on the oxide layer. A process for production of the calcium phosphate-coated composite material is also disclosed.

This is a division of application Ser. No. 07/109,887, filed Oct. 19,1987 now U.S. Pat. No. 4,847,163.

FIELD OF THE INVENTION

The present invention relates to a composite material comprising ametallic substrate coated with calcium phosphate which is excellent inaffinity to the tissue of bone or teeth, which is thus useful as animplant material such as artificial bone, teeth and teeth roots, or as abonding material for such implant materials, and a process forproduction thereof.

BACKGROUND OF THE INVENTION

A living body implant material such as artificial bone and an artificialtooth root has been receiving great attention in recent years becausewhen the bone is broken and lost by an accident, for example, or thetooth is taken out, it can be restored by bonding the implant materialor planting the implant material in the jaw bone, and thus the bone ortooth can be used in the nearly original form and a comforable life canbe enjoyed. Since, however, the implant material is embedded in theliving body, it is essential that the material be harmless to the humanbody and it must satisfy such requirements as sufficiently highstrength, good processability, no dissolution, suitable specific densityand good affinity to the living body.

Metals such as noble metals, alloys such as stainless steel, ceramicssuch as α-alumina, and in addition, apatite have heretofore been used asan implant material. These materials, however, have at least one of suchdisadvantages as toxicity is exhibited, the strength is insufficientlylow, the processability is poor, dissolution occurs, and affinity to theliving body is poor.

In order to eliminate the above disadvantages, it has been desired todevelop metals or ceramics which when coated on the surface withapatite, provide a composite material having good affinity to the livingbody. For this purpose, a technique to bond metal and ceramic, or tobond ceramic and ceramic is needed. As such a metal-ceramic bondingtechnique or ceramic-ceramic bonding technique, only a plasma spraycoating method has been known. Further this plasma spray coating methodhas disadvantages in that the yield of expensive apatite particles islow and the bonding between the coating and the substrate is not alwayssufficiently high. Moreover, if the plasma spray coating method isapplied under too severe conditions, partial decomposition occurs duringthe spray coating process and it becomes necessary to conduct additionaltreatments such as crystallization.

In order to overcome the above prior art problems, the present inventorswith another has proposed an implant material in which a metallicsubstrate and a coating of calcium phosphate are firmly bonded with anintermediate layer containing calcium phosphate sandwiched therebetween(Japanese Patent Application Nos. 64012/86, 64013/86 and 70504/86(corresponding to U.S. patent application Ser. No. 29,519 filed Mar. 24,1987)), and an implant material in which a metallic substrate and acoating of calcium phosphate are bonded together with no intermediatelayer sandwiched therebetween (Japanese Patent Application No. 169547/86(corresponding to U.S. patent application Ser. No. 74837 filed Jul.17,1987)), and moreover all can be produced without the use of the spraycoating method.

In these implant materials, the bonding strength between the metallicsubstrate and the coating of calcium phosphate is sufficiently high.However, when they are embedded in the living body, the coating ofcalcium phosphate having good affinity to the bone tissue may assimilatewith the bone tissue, finally bringing the metallic substrate in directcontact with the bone tissue. Since the affinity of the metallicsubstrate to the bone tissue is poor, the bone tissue regresses, therebydegrading the bonding between the bone tissue and the metallicsubstrate, and in the worst case, the implant material may be rejected.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a composite materialwhich is good in workability, is of sufficiently high mechanicalstrength, has increased affinity to the bone tissue, and can maintainstable bonding properties over a long time, and thus which is suitableas an implant material such as an artificial bone and an artificialtooth root, and also a process for production of the composite material.

The present invention relates to a calcium phosphate-coated compositematerial comprising a metallic substrate, an oxide layer on the metallicsubstrate, the oxide layer consisting essentially of an oxide of one ormore metals selected from the group consisting of titanium, zirconium,hafnium, vanadium, niobium, tantalum, tin, cobalt, aluminum, chromium,molybdenum and tungsten, and a coating of calcium phosphate provided onthe oxide layer.

The present invention also relates to a process for producing a calciumphosphate-coated composite material which comprises coating a coatingsolution containing one or more metals selected from the groupconsisting of titanium, zirconium, hafnium, vanadium, niobium, tantalum,tin, cobalt, aluminum, chromium, molybdenum and tungsten on the surfaceof a metallic substrate, heating the resulting coating in an oxidizingatmosphere to convert the metal into the corresponding oxide and to forma layer consisting essentially of the oxide, and then forming a coatingof calcium phosphate on the surface of the oxide layer.

The major feature of the present invention resides in the fact that theoxide layer of metal oxide having relatively good affinity to the livingbody and sufficiently high corrosion resistance is sandwiched betweenthe metallic substrate and the coating of calcium phosphate, so thateven when the coating of calcium phosphate surface layer is absorbed inthe bone tissue, direct contact between the metallic substrate and thebone tissue can be prevented and thus degradation of the bondingproperties between the metallic substrate and the bone tissue can beprevented.

DETAILED DESCRIPTION OF THE INVENTION

The present invention will hereinafter be explained in detail.

The present invention provides a calcium phosphate-coated compositematerial comprising a metallic substrate, an oxide layer on the metallicsubstrate, said oxide layer consisting essentially of the oxide ofmetals such as titanium, having excellent corrosion resistance in theliving body and exhibiting good adhesion properties to the metallicsubstrate, and a coating of calcium phosphate on the oxide layer, whichis suitable as an implant material, and a process for producing thecalcium phosphate-coated composite material. In accordance with thepresent invention, there can be provide a composite material which canbe bonded to a bone, for example, with sufficiently high affinity in theliving body and moreover exhibit stable bonding properties over a longtime.

The metallic substrate as used herein means a substrate made of metalssuch as titanium, titanium alloys and stainless steel which are stablein the living body. The titanium and titanium alloys include metallictitanium and titanium alloys of titanium and Ta, Nb, platinum groupmetals, Al, V and so on. The stainless steel as used herein includes, aswell as so-called stainless steel such as JIS (Japanese IndustrialStandards) SUS 304, 310 and 316, corrosion resistant alloys such as acobalt-chromium alloy for implanting into the living body. The metallicsubstrate made of the metal as described above may be in the form ofe.g., a plate and a bar, may be smooth on the surface, may have a poroussurface like a sponge, or may be an expanded mesh or a porous plate. Thereason why the metals as described above are used as the substrate isthat the metals have a sufficiently high mechanical strength and can beeasily molded in comparison with sintered materials and glass.

The surface of the metallic substrate may be previously subjected to arinsing treatment such as washing with water, acid, supersonic waves,steam and so on, to remove impurities thereon and to increase theaffinity to the oxide layer as described hereinafter. If desired, thesurface of the metallic substrate may be made coarse by applying a blastand/or etching treatment to increase the affinity to the oxide layer andat the same time, to conduct activation. The above etching includes, aswell as chemical etching, physical etching such as sputtering.

On the above-described metallic substrate, the oxide layer of metaloxide is formed. The oxide layer consists essentially of the oxide ofone or more metals selected from the group consisting of titanium,zirconium, hafnium, vanadium, niobium, tantalum, tin, cobalt, aluminum,chromium, molybdenum and tungsten. Examples of such metal oxides areTiO₂, ZrO₂, HfO₂, VO₂, V₂ O₅, Nb₂ O₅, NbO₂, TaO₂, Ta₂ O₅, Cr₂ O₃, Mo₂ O,MoO₃, WO₃, SnO₂, Co₂ O₃, Co₃ O₄, CoO, Al₂ O₃ and their mixtures or solidsolutions. In addition, the oxide layer may contain oxides in theso-called suboxide state resulting from removal of part of the oxygen inthe oxide, composite oxides resulting from dissolution of the metallicsubstrate component, composite oxides with the calcium phosphate coatingas the upper layer, and moreover undecomposed or half-decomposedproducts of the components in the coating solution.

The oxides of titanium, zirconium, hafnium, niobium, tantalum, tin,chromium, molybdenum and tugsten as obtained by the thermaldecomposition method as described hereinafter are excellent in corrosionresistance, particularly acid resistance, and thus can be usedindependently. However the stability of the solution containing thesalts of the above metals as described hereinafter is poor. This poorstability can be improved by adding elements having a valence numberdifferent from that of the component element. For example, an alcoholsolution of tungsten chloride having a valence of 6 is easily hydrolyzedby moisture in the air and its color changes from light yellow to blackpurple. This color change can be considerably inhibited by adding asmall amount of tantalum alkoxide having a valence of 5. An alcoholsolution of titanium alkoxide having a valence of 4 is easily hydrolyzedby moisture in the air and becomes turbid or forms white precipitates.The alcohol solution can be maintained in a stable condition for a longtime by adding a small amount of vanadium alkoxide having a valence of5.

In the lower layer of the oxide layer subjected to thermal decompositionin an oxidizing atmosphere, an oxide coating of the substrate componentor a layer of a mixture or solid solution of the oxide of the substratecomponent with the metal oxide of the oxide layer is formed. If theoxide layer subjected to thermal decomposition contains the samecomponent as in the oxide layer of the substrate component, a completelycontinuous mixed oxide or solid solution layer can be formed. Forexample, if chromium is added to the coating solution, when stainlesssteel is used as the substrate, an oxide layer which is continuous inchromium density to the chromium oxide surface layer can be formed andthus a more increased bonding strength can be obtained. In the case ofan Fe-Cr-AI alloy, since an alumina coating is formed on the surface, itis sufficient to add alminum to the coating. Also in the case of a Co-Cralloy, it suffices that cobalt or chromium is added.

To form the oxide layer on the metallic substrate, it suffices that asolution containing the metal salt is coated on the metallic substrate,dried and then calcined by heating in an oxidizing atmosphere to convertthe metal salt into the corresponding oxide and at the same time, tofirmly bond it to the surface of the metallic substrate. In a case wherethe metallic substrate is made titanium or a titanium alloy, ahydrochloric acid aqueous solution or alcohol solution of e.g., thechloride or alkoxymetal salt of the above metal is used as the coatingsolution, which is coated on the surface of the metallic substrate whichhas been activated by applying pre-treatment, dried and then heated inan oxidizing atmosphere, for example, at 300° to 700° C. for 5 to 30minutes, whereupon there can be obtained a metal oxide layer firmlybonded to the metallic substrate. The reason why the above hydrochloricacid aqueous solution or alcohol solution is preferably used as thecoating solution is that they corrode titanium to some extent at hightemperatures and form fine irregularities in the surface of the metallicsubstrate, thereby further improving the bonding properties between themetallic substrate and the oxide layer.

The oxidizing atmosphere as used herein means an atmosphere containing asufficient amount of oxygen to convert the metal into the correspondingmetal oxide. It is usually sufficient to use air as the oxidizingatmosphere. Preferably, heating is carried out in a muffle furnace.

In the case where the metallic substrate is made of an anti-corrosivealloy such a stainless steel, if the coating solution contains halogenions or a halogen compound, when the coating solution is coated andcalcined, part of the halogen remains in the coating in the form ofoxychloride or free halogen and, as a result, the problem of corrosionof the metallic substrate which is not encountered in the case oftitanium or titanium alloy occurs and may cause separation of thecoating. In this case, therefore, it is necessary to use a coatingsolution not containing a halogen. Preferred coating solutions includean aqueous solution of nitric acid salts and a non-aqueous solution oforganic metals which are able to slightly corrode the metallic substrateat the time of calcination as in the case of titanium or a titaniumalloy, thereby increasing the bonding properties between the metallicsubstrate and the oxide layer.

The coating solution is coated on the metallic substrate by any desiredmethod such as brush coating and soaking of the metallic substrate inthe coating solution, and then calcining in an oxidizing atmospherepreferably at 300° to 800° C. for 5 to 30 minutes. When a coatingsufficiently large in thickness cannot be obtained by only one coatingand calcination procedure, the procedure can be repeated until thedesired thickness can be obtained.

On the oxide layer thus provided on the metallic substrate is thenformed a coating of calcium phosphate. The calcium phosphate as usedherein mainly means apatite hydroxide and additionally includestricalcium phosphate, calcium hydrogenphosphate and calciumdihydrogenphosphate which are considered to be by-produced at the timeof calcination of apatite hydroxide, and calcium phosphate-basedcompounds formed from apatite hydroxide and impurity components orcomponents of the oxide layer.

The method of forming the coating and conditions under which the methodis carried out are not critical. Typical methods include a plasma spraycoating method and a thermal decomposition method.

The plasma spray coating method has an advantage of being able to easilyform the coating although it suffers from disadvantages in that it needsexpensive apatite hydroxide and the yield is not sufficiently high. Whenspray coating is applied directly onto the metal, it should be carriedout under severe conditions in order to obtain satisfactory bondingproperties, and such severe conditions cause partial decomposition ofthe expensive apatite hydroxide. In the present invention, on the otherhand, since the coating of calcium phosphate is formed on the oxidelayer, sufficiently satisfactory bonding properties can be obtained evenif spray coating is applied under such conditions as not to causedecomposition of apatite hydroxide.

It suffices that the spray coating is carried out in an atmospherecomprising argon gas and hydrogen and the electric power is about 30 kW.The particle diameter of apatite hydroxide is preferably intermediate insize, for example from about 125 to 345 mesh.

In the case of the thermal decomposition method, a nitric acid aqueoussolution in which calcium phosphate, preferably apatite hydroxide isdissolved and preferably saturated is coated on the surface of the oxidelayer and then calcined to form a coating layer having good bondingproperties to the oxide layer on the metallic substrate. In this case,the calcination product is mainly a calcium phosphate compoundcomprising apatite hydroxide. The optimum calcination conditions varywith the solution, particularly the nitric acid concentration. As thenitric acid concentration is increased, the optimum temperature isincreased. The optimum temperature is 350° to 500° C. at 10% nitric acidand 450° to 800° C. at 60% nitric acid. The calcination temperature ispreferably in the range of 300° to 800° C. If the calcinationtemperature is less than 300° C., the coating of calcium phosphate isinsufficiently low in strength. On the other hand, if it is more than800° C., the metallic substrate is seriously oxidized and the separationof the oxide layer from the metallic substrate easily occurs. Althoughthe calcination can be carried out in an oxidizing atmosphereexemplified by air, it is preferred to be carried out in an inertatmosphere exemplified by argon.

The coating layer can also be formed by coating a solution of a mixtureof calcium carbonate and calcium phosphate in a suitable ratio and thencalcinating in an oxidizing or inert atmosphere. In this case, it ispreferred that hydrothermal treatment be applied to increasecrystallinity.

In accordance with the above procedures, there can be obtained animplant material which is good in workability, is sufficiently high inmechanical strength, has increased affinity in the bone tissue andliving body, and can hold stable bonding properties to the living bodyover a long time.

The present invention is described in greater detail with reference tothe following examples although it is not intended to be limitedthereto.

Unless otherwise specified, all rates, percents, etc. are by weight.

EXAMPLE 1

A 40 mm×20 mm piece was cut out of a JIS No. 1 titanium rolled sheethaving a thickness of 1 mm. The surface of the piece was made coarse byapplying blast treatment with a #80 steel shot, and then washed bysoaking in a 25% sulfuric acid aqueous solution maintained at 90° C. for30 minutes. This piece was used as a substrate. On this titaniumsubstrate, a 10% hydrochloric acid solution of a mixture of tantalumchloride containing 10 g/l of tantalum and titanium chloride containing10.4 g/l of titanium was coated and dried, which was then calcined in amuffle furnace maintained at 450° C. for 10 minutes. The above procedurewas repeated to form an intermediate oxide layer of 1.0×10⁻² mol/m² of atitanium oxide-tantalum oxide (TiO₂ -Ta₂ O₅) mixed oxide (molar ratio ofTi to tantalum: 80:20). The apparent thickness of the oxide layer wasabout 0.3 μ m.

About 3 g of apatite hydroxide power was gradually added to 10 g of a25% aqueous nitric acid solution while fully stirring to prepare acoating solution. This coating solution was coated on the oxide layer ofthe titanium substrate, which was immediately placed in a stream ofargon and dried at 60° C. for 20 minutes, and then calcined by heatingat 500° C. for 10 minutes in the same atmosphere as above. This heatcalcination procedure was further repeated twice. A white coating formedon the surface was very firmly bonded to the underlying titaniumsubstrate, X-ray diffraction confirmed that it was apatite hydroxidehaving good crystallinity.

EXAMPLE 2

A 40 mm×20 mm piece was cut out of a stainless steel SUS 316L rolledsheet having a thickness of 1 mm. The surface of the piece was madecoarse by applying blast treatment with a #70 corrondum grid and furtherwashed by soaking in a 30% aqueous FeCl₃ solution at 25° C. for 4minutes. This piece was used as a substrate. On this stainless steelsubstrate, a butanol solution of niobium ethoxide and titanium ethoxide(niobium: 5.1 g/l; titanium: 10.5 g/l) was coated and dried, which wasthen calcined in a muffle furnace maintained at 450° C. for 10 minutes.This procedure was repeated twice to form an intermediate oxide layer of1.0×10⁻² mol/m² of a titanium oxide-niobium oxide (TiO₂ -Nb₂ O₅) mixedoxide (molar ratio of titanium to niobium, 80:20).

About 3 g of apatite hydroxide powder was added to 10 g of a 25% nitricacid aqueous solution to prepare a coating solution. This coatingsolution was coated on the oxide layer of the stainless steel substrate,dried in a stream of argon at 60° C. for 20 minutes, and furthercalcined by heating in the same atmosphere as above at 500° C. for 10minutes. This heat-calcination procedure was further repeated twice. Awhite coating layer formed on the surface was firmly bonded to theunderlying stainless steel substrate. X-ray diffraction confirmed thatit was apatite hydroxide having good crystallinity.

EXAMPLE 3

On a JIS No. 1 titanium rolled sheet was formed an intermediate oxidelayer of 1.0×10⁻² mol/m² of a mixed oxide of titanium oxide-tantalumoxide (TiO₂ -Ta₂ O₅) (molar ratio of titanium to tantalum, 80:20) underthe same conditions as in Example 1.

On the oxide layer, apatite hydroxide granules adjusted in particle sizeto about 125 to 345 mesh were plasma spray-coated under conditions asshown in Table 1. A white coating layer formed on the surface was veryfirmly bonded to the underlying titanium substrate. X-ray diffractionanalysis confirmed that it was apatite hydroxide having goodcrystallinity.

                  TABLE 1                                                         ______________________________________                                        Flow Rate of Plasma Gas                                                       Ar                    30     l/min                                            H.sub.2               6      l/min                                            Flow Rate of Carrier Gas                                                                            6      l/min                                            Arc Voltage (DC)      60     V                                                Arc Current (DC)      500    A                                                Spraying Distance     100    mm                                               ______________________________________                                    

Some of the advantages of the present invention are described below.

(1) Since corrosion resistant titanium, titanium alloys or stainlesssteel are used as the metallic substrate and the metal oxide layer isformed on the surface of the metallic substrate, the composite materialof the present invention, when used as an artificial bone or artificialtooth root, is harmless to the living body, is stable, is almost free ofthe possibility of dissolution, and further is sufficiently high inmechanical strength and is easily worked.

(2) Since the surface of the metallic substrate is covered with acalcium phosphate compound exemplified by apatite hydroxide, thecomposite material of the present invention exhibits sufficiently highaffinity in the living body and thus can be bonded to the bone in theliving body with ease and further with high strength.

(3) Since, as described above, the metal oxide layer is formed on thesurface of the metallic substrate, even when the calcium phosphateparticularly excellent in affinity is absorbed in the bone tissue over along time after implantation in the living body, the oxide layer formedon the metallic substrate prevents the metallic substrate from cominginto direct contact with the bone tissue and also prevents degradationof bonding properties between them as based on insufficient affinitybetween the bone tissue and the metallic substrate. Thus the calciumphosphate-coated composite material of the present invention can be usedas an implant material without causing any change in the stabilitythereof for a long time.

(4) Since the metal oxide layer is formed between the calcium phosphatecoating and the metallic substrate and the coating can be firmly bondedon the metal oxide layer by plasma spray coating even under relativelymild conditions, the coating layer can be formed easily and it becomespossible to employ the spray coating method which has not been employedbecause of decomposition of apatite hydroxide.

While the invention has been described in detail and with reference tospecific embodiments thereof, it will be apparent to one skilled in theart that various changes and modifications can be made therein withoutdeparting from the spirit and scope thereof.

What is claimed is:
 1. A process for producing a calcium phosphate coated-composite material which comprises coating a coating solution containing one or more metals selected from the group consisting of titanium, zirconium, hafnium, vanadium, niobium, tantalum, tin, cobalt, aluminum, chromium, molybdenum and tugsten on the surface of a metallic substrate, converting the one or more metals into a corresponding oxide by heating in a oxidizing atmosphere to form an oxide layer, and then forming a coating of calcium phosphate on the surface of the oxide layer.
 2. The process as claimed in claim 1, wherein the metallic substrate is made of titanium or a titanium alloy.
 3. The process as claimed in claim 1, wherein the metallic substrate is made of a corrosion resistant iron alloy and the coating solution is a solution containing neither halogen ions nor halogen compounds.
 4. The process as claimed in claim 1, wherein the formation of the oxide layer by heat treatment is carried out by calcinating at a temperature not less than 300° C.
 5. The process as claimed in claim 2, wherein the formation of the oxide layer by heat treatment is carried out by calcinating at a temperature not less than 300° C.
 6. The process as claimed in claim 3, wherein the formation of the oxide layer by heat treatment is carried out by calcinating at a temperature not less than 300° C.
 7. The process as claimed in claim 1, 2, 3, 4, 5 or 6, wherein the coating of calcium phosphate is carried out by plasma spray coating of calcium phosphate and/or apatite hydroxide power.
 8. The process as claimed in claim 1, 2, 3, 4, 5 or 6, wherein the coating of calcium phosphate is carried out by coating a nitric acid aqueous solution of apatite hydroxide as a coating solution on the surface of the oxide layer, and then calcining the coating solution at a temperature not less than 300° C. 